The difficulty quitting and chronic relapse which characterize the experience of many smokers may be due in large measure to the adaptations in neural mechanisms regulating reward, affect, and goal- directed behavior that have taken place as a consequence of repeated drug use. Recent theoretical formulations of nicotine dependence have suggested that these motivational systems have been compromised in ways that bias the individual's cognitive resources and behavior towards smoking, even with the explicit goal to quit. Cognitive control in general and error monitoring specifically is critical to overcoming the potent neural mappings that drive smoking behavior under these conditions. The specific aims of this proposal are to study neural substrates related to error monitoring in a sample of smokers attempting to quit using behavioral counseling and the transdermal nicotine patch. This study will utilize electrophysiological (dense sensor array EEG recording) to measure the error-related negativity (ERN), an event-related potential likely generated in the anterior cingulate cortex (ACC) and related areas of the pre-frontal cortex that occurs following a response error. Studies suggest that the ERN directly reflects the activity of mesolimbic dopamine neurons, whose firing patterns activate/inhibit the ACC and encode events as events as being "worse" (making an error) or "better" (receiving a reward) than expected. Smokers interested in quitting will participate in two counterbalanced laboratory sessions (one deprived and one non-deprived) prior to their quit date in which they will complete a modified 2-choice flanker task. Each trial will be followed by feedback indicating whether the participant initiated a correct, incorrect, or late response. In half of the trials, correct trials will be followed by positively motivating images (pictures of erotic couples) and incorrect by neutral images (pictures of animals);in the other half, correct responses will be followed by neutral images (plants) and incorrect by negatively motivating images (mutilations). Smokers will enter smoking cessation therapy consisting of counseling and nicotine replacement following the second EEG assessment. The design will enable us to tease apart the relative impact of approach (reward) and avoidance motivation on the efficiency of the behavioral (error) monitoring system and its relation to abstinence. We predict that nicotine deprivation will alter the effects of the ERN: potentially increasing error monitoring on positive trials and/or decreasing error monitoring on negatively motivating trials. It is expected that individuals showing the smallest decrease in the ERN between either deprivation or motivational conditions will have higher abstinence rates at the end of treatment. The results of this study will improve our understanding of the neurobiological systems associated with reward, affect, and cognitive control among smokers by informing theory and potentially contributing to future interventions aimed at normalizing these systems during cessation. PUBLIC HEALTH RELEVANCE: The difficulty quitting and chronic relapse which characterize the experience of many smokers may be due in large measure to the adaptations in neural mechanisms regulating reward, affect, and goal-directed behavior that have taken place as a consequence of repeated drug use. This study will use the ERN (error related negativity) component of the ERP (event related potential) to determine the relative impact of approach (reward) and avoidance motivation on the efficiency of the behavioral (error) monitoring system and its relation to abstinence. We predict that nicotine deprivation will alter the effects of the ERN: potentially increasing error monitoring on positive trials and/or decreasing error monitoring on negatively motivating trials. It is expected that individuals showing the smallest decrease in the ERN between either deprivation or motivational conditions will have higher abstinence rates at the end of treatment. The results of this study will improve our understanding of the neurobiological systems associated with reward, affect, and cognitive control among smokers by informing theory and potentially contributing to future interventions aimed at normalizing these systems during cessation.